Patients with coronary artery disease (CAD) who experience disabling angina despite attempts at revascularization are encountered with increasing frequency. We hypothesized that cytokine mobilization of stem and progenitor cells from bone marrow may promote myocardial neovascularization with relief of ischemia and improvement in symptoms. We administered granulocyte colony-stimulating factor (G-CSF) 10 microg/kg/day for 5 days to 16 symptomatic patients with inducible ischemia despite prior attempts at revascularization. G-CSF increased CD34+/CD133+ cells from 1.5?0.2 to 52.4?10.4/microL (P<0.001), indicating mobilization of cells with endothelial progenitor potential. Indices of platelet and coagulation activation were not changed by treatment, but C-reactive protein (CRP) increased from 4.5?1.3 to 8.6?1.3 mg/L (P=0.017). Two patients experienced serious adverse events: 1) non-ST elevation myocardial infarction (MI) 8 hours after the fifth G-CSF dose, and 2) MI and death 17 days after treatment. At 1 month post-treatment, there was no improvement from baseline values (i.e., reduction) in the MRI-determined composite wall motion score (from 25.7?2.1 to 28.3?1.9, P=0.20) and a trend towards a greater number of ischemic segments (from 4.5?0.6 to 6.1?1.0, P=0.068) during dobutamine stress. There was no improvement in treadmill exercise duration (modified Bruce protocol) at 1 month (12.2?0.7 min, P=0.37), and in 12 patients at 3 months (11.4?0.9 min, P=0.98), compared with baseline measurements (11.9?0.9 min). Conclusions- G-CSF administration to CAD patients mobilizes progenitor cells from bone marrow, but without objective evidence of cardiac benefit. Significant increases in CRP may destabilize plaques and contribute to adverse outcomes during treatment in some patients.